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- Title
Hypoxia interferes with aryl hydrocarbon receptor pathway in hCMEC/D3 human cerebral microvascular endothelial cells.
- Authors
Jacob, Aude; Potin, Sophie; Saubaméa, Bruno; Crete, Dominique; Scherrmann, Jean‐Michel; Curis, Emmanuel; Peyssonnaux, Carole; Declèves, Xavier
- Abstract
The expression of aryl hydrocarbon receptor (AhR) transcription factor was detected at transcript level in freshly isolated human brain microvessels and in the hCMEC/D3 human cerebral microvascular endothelial cell line. Recent studies have demonstrated that AhR pathway is able to crosstalk with other pathways such as hypoxia signaling pathway. Therefore, we used the hCMEC/D3 cell line to investigate the potential crosstalk between AhR and hypoxia signaling pathways. First, we performed two different hypoxia-like procedures in hCMEC/D3 cells; namely, exposition of cells to 150 μM deferoxamine or to glucose and oxygen deprivation for 6 h. These two procedures led to hypoxia-inducible factor (HIF)-1a and HIF-2a proteins accumulation together with a significant induction of the two well-known hypoxia-inducible genes VEGF and GLUT-1. Both HIF-1a and -2a functionally mediated hypoxia response in the hCMEC/D3 cells. Then, we observed that a 6 h exposure to 25 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin, a strong AhR ligand, up-regulated CYP1A1 and CYP1B1 expression, and that this effect was AhR dependent. Regarding AhR and hypoxia crosstalk, our experiments revealed that an asymmetric interference between these two pathways effectively occurred in hCMEC/D3 cells: hypoxia pathway interfered with AhR signaling but not the other way around.
- Subjects
ENDOTHELIAL cells; HYPOXEMIA; ARYL hydrocarbon receptors; GENE expression; TRANSCRIPTION factors; CELLULAR signal transduction
- Publication
Journal of Neurochemistry, 2015, Vol 132, Issue 4, p373
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.12972